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CN1091602C - Peritoneal dialysis solutions containing maltodextrins and amino acids - Google Patents

Peritoneal dialysis solutions containing maltodextrins and amino acids Download PDF

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CN1091602C
CN1091602C CN95190042A CN95190042A CN1091602C CN 1091602 C CN1091602 C CN 1091602C CN 95190042 A CN95190042 A CN 95190042A CN 95190042 A CN95190042 A CN 95190042A CN 1091602 C CN1091602 C CN 1091602C
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solution
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peritoneal dialysis
dialysis solution
aminoacid
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CN1122106A (en
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L·马蒂斯
R·布克
T·索克利
L·W·亨德森
B·法勒
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Baxter International Inc
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
    • A61M1/28—Peritoneal dialysis ; Other peritoneal treatment, e.g. oxygenation
    • A61M1/287—Dialysates therefor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides

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Abstract

A peritoneal dialysis solution comprising as osmotic agents approximately 2.0 to about 6.0 % (w/v) maltodextrins and approximately 0.25 to about 2.0 % (w/v) amino acids. The peritoneal dialysis solution will also include other components such as sodium, chloride, lactate, bicarbonate, calcium, and magnesium.

Description

Contain maltodextrin and amino acid whose peritoneal dialysis solution
Technical background
The present invention relates generally to peritoneal dialysis.Relate in particular to peritoneal dialysis solution.
As everyone knows, use dialysis can keep renal failure no longer possesses enough functions to kidney patient.Use two kinds of main dialysis process to be hemodialysis and peritoneal dialysis.Hemodialysis utilizes the hemodialyzer dialysis machine, makes patient's blood flow through this machine.Diaphragm in the machine plays hemodialyzer effect and blood clean.Hemodialysis is kind of an external disposal, requires special machine.Therefore, hemodialysis has its inherent shortcoming.
The progress of peritoneal dialysis has overcome some shortcoming of hemodialysis.In the peritoneal dialysis, the peritoneum that the patient controls oneself is as semipermeable membrane.Because the nexine at this film of body cavity exists a large amount of blood vessels and blood capillary, peritoneum can play natural semipermeable membrane.
During peritoneal dialysis, utilize conduit that dialysis solution is imported the abdominal cavity.After the enough time, obtained the exchange of solute between dialysis solution and the blood.By the suitable osmotic gradient mode of autoblood to dialysis solution is provided, obtained fluidic removal, make water flow out blood.This just makes blood recover the suitable balance of soda acid, electrolyte and fluid, and make dialysis solution by conduit by simply from the body cavity drain.
Peritoneal dialysis has many advantages.Yet one of difficulty that runs into provides a kind of dialysis solution that comprises suitable penetrating agent.Needed is to obtain enough osmotic gradients.Then to use penetrating agent for obtaining this osmotic gradient.Penetrating agent is kept needed osmotic gradient, water and noxious substance is transported by peritoneum enter dialysis solution.
For making it suitable, penetrating agent need satisfy at least one pair of standard.At first, it must be nontoxic and be any biological inert basically.But this reagent should be metabolizable.This reagent should not see through peritoneum soon and enter blood.Based on satisfying this two standards, people can allow maximum ultrafiltration gradient be kept, and can prevent that also toxin or unwanted material from accumulating in blood.
Can think that with regard to the penetrating agent in the percolating solution, neither one now can satisfy this standard with material at present.The most widely used current penetrating agent is dextrorotation (Fructus Vitis viniferae) sugar.Dextrose is quite safe, and is easy to metabolism after entering blood.
But being to use one of problem that dextrose runs into is that it is absorbed in dialysis solution by blood soon.Because it is so fast that dextrose passes peritoneum, make and inject osmotic gradient dissipation within two to three hours.This will cause ultrafiltration direction reversing, makes water be absorbed in dialysis solution during terminal in this exchange is allowed time again.
Another problem that relates to dextrose is, because it soon by blood absorption, includes energy in with just representing patient's vast scale.To the non-diabetic patient, this problem is not obvious.Yet to glucose tolerance patient in damaged condition, this just is expressed as serious metabolism burden.Dextrose also can cause many problems to hyperglycemia or fat patient.
Another problem that runs into dextrose relates to the preparation of dialysis solution.Dialysis solution is analogous to other medical articles and solution, sterilizes to heat usually.Undesirablely be to make this sugar caramelization at the dextrose heat sterilization of physiological PH value.For remedying this problem, known method is that the pH value with dialysis solution is adjusted within the 5-5.5 scope, and at this low pH value, the dextrose caramelization reduces to minimum during heating.Yet can believe that this low pH value stands the fashionable meeting of dialysis fluid flow some patient and causes pain.In addition, low pH value solution can cause other problems, for example can influence peritoneum host protection.
For solving more above-mentioned problems, proposed that many materials replace dextrose.Can think the existing suitable succedaneum that is proved to be dextrose with neither one in the material of proposal.
Dextran, polyanion and glucose polymer have been proposed alternative dextrose.Because their high molecular can think that they should be reduced to minimum through the diffusion that peritoneum enters blood.But it must be high concentration (W/V) in dialysis fluid that the hyposmosis activity of these materials of per unit quantity requires this material, in order that make it effective.In addition, the system of these materials absorbs, and mainly by lymph, but is accompanied by slow metabolism, and this has just increased the serious problems of these reagent long-term safeties.
Also explored small molecular weight material.These materials comprise glycerol, Sorbitol, xylitol and fructose.But, think that these materials cause many safety issues, do not provide substantial advantage simultaneously above dextrose.
To the attractive succedaneum of dextrose is aminoacid.Recent research shows that aminoacid has good drug-resistant capability.But because its low-molecular-weight, they by peritoneum, cause osmotic gradient to disappear fast very fastly.In addition, amino acid whose quick picked-up causes huge nitrogen load, and amino acid whose use is limited to changes every day one twice.
Recently, having explored polypeptide is the potential penetrating agent of a class.Should believe that polypeptide will pass through peritoneum lentamente, therefore between dialysis solution and blood, keep a kind of osmotic gradient of prolongation.People's such as Gilchrist US4906616 and the EP of Klein 0218900 disclose polypeptide and be used as penetrating agent in peritoneal dialysis solutions.Each of these patents is all discussed the Dai Pin of the polypeptide of dextrose.As disclosed, polypeptide only is that penetrating agent is used in these prescriptions.
Should believe that the polypeptide solution of people such as Gilchrist and Klein suggestion has very limited clinical practice.As aminoacid, though size is bigger, these peptide compositions are absorbed from peritoneum soon.This can cause uraemic syndrome.In addition, these materials that contain polypeptide have the anaphylactoid potential ability of generation.This is because the size of used polypeptide.
Also having explored glucose polymer is used in the peritoneal dialysis solution.US4761237 discloses glucose polymer has been used for dialysis solution.EP 0076355 disclosed dialysis solution comprises in conjunction with the conventional electrolysis matter of sodium, calcium, magnesium, chloride, lactate and sodium hydroxide with comprising the what is called improvement thing of glucose polymer as penetrating agent.The penetrating agent that EP 0153164 disclosed peritoneal dialysis solution contains is a kind of mixture of glucose polymer.Can thinking US4886789 and EP 0153164, the two is relevant.
Can think that disclosed solution does not solve above-mentioned all problems.
Therefore the peritoneal dialysis solution that needs a kind of improvement.
Brief summary of the invention
The invention provides a kind of dialysis solution of improvement.The dialysis solution of this improvement provides a kind of mixture of aminoacid and maltodextrin to be used as penetrating agent in peritoneal dialysis solution.
For this purpose, in embodiments, peritoneal dialysis solution provided by the invention comprises the maltodextrin of about 2-6% (w/v) and approximately necessary aminoacid and the nonessential amino acid whose mixture of 0.25-2% (w/v) are used as penetrating agent.
In a kind of embodiment, aminoacid comprise must aminoacid and nonessential aminoacid both.
In a kind of embodiment, described solution comprises: the sodium of 120-about 140 (mEq/L), the chloride of 70-about 110 (mEq/L), the lactate of 0-about 45.00 (mEq/L), the bicarbonate of 0-about 45.00 (mEq/L), the calcium of 0-about 4.00 (mEq/L), the magnesium of 0-about 4.00 (mEq/L).
In a kind of embodiment, maltodextrin is derived by the starch hydrolysis and is had following the composition:
Weight average molecular weight (Mw) 10000-16000 dalton
Number-average molecular weight (Mn) 4000-8000 dalton dispersion polymerization 1.0-4.0 fraction＞100000 dalton NMT are 1.0% single, two, trisaccharide NMT 5.0% distribute normal α (1-4) NLT 90% aluminium (10% solution)＜10ppb water solubility NLT 10% (w/v) pH (10% solution) 5.0-7.0 heavy metal＜5ppmDP (degree of polymerization) greater than 20 〉=75%DP greater than 50 〉=50%DP greater than 100 〉=25%
In a kind of embodiment, aminoacid comprises:
Amino acid concentration (mg%)
Leucine 74-112
Valine 100-151
Threonine 47-71
Isoleucine 61-92
Lysine hydrochloride 55-83
Histidine 52-78
Methionine 32-48
Phenylalanine 42-62
Tryptophan 20-30
Alanine 68-103
Proline-4 3-65
Arginine 60-113
Glycine 36-55
Serine 48-72
Tyrosine 20-35
Aspartic acid 55-83
Threonine 55-83
In a kind of embodiment, aminoacid is selected following ratio:
Phenylalanine/tyrosine 1.3-3.0
Necessary/total amount aminoacid 0.4-0.7
In a kind of embodiment, maltodextrin and aminoacid constitute unique penetrating agent in solution.In another embodiment, the peritoneal dialysis solution that provides comprises:
Maltodextrin (%w/v) 2.0-6.0
Aminoacid (%w/v) 0.25-2.0
Sodium (mEq/L) 120-140
Chloride (mEq/L) 70-110
Lactate (mEq/L) 0.0-45.0
Bicarbonate (mEq/L) 0.0-45.0
Calcium (mEq/L) 0.0-4.0
Magnesium (mEq/L) 0.0-4.0
pH 6.0-7.4
In a kind of embodiment, a kind of method of the penetrating agent that obtains being used for peritoneal dialysis solution is provided, comprise and select the step of two kinds of components as penetrating agent, the weight average molecular weight that a kind of component has is equal to or greater than 10000 dalton and constitutes about 2.0-6.0% (w/v) of said composition, and the molecular weight that second kind of component has is equal to or less than 300 dalton and constitutes about 0.25-2.0% (w/v) of said composition.
In a kind of embodiment of method, penetrating agent comprises maltodextrin and aminoacid.
In other embodiment, provide and carried out the peritoneal dialysis solution that blended two parts are set before the patient injects, it comprises: the first of taking in first kind of device comprises about 2.0-6.0% (w/v) maltodextrin and the about 4.0-5.5 of pH value; The second portion of taking in second kind of device comprises aminoacid; Not only can but also can in second kind of device, comprise the following ingredients of q.s at first kind of device, like this, it is as follows to obtain ingredients when first and second portion mixing: the sodium of 120-about 140 (mEq/L), the chloride of about 70.0-110.00 (mEq/L), the lactate of about 0.0-45.0 (mEq/L), the bicarbonate of about 0.0-45.0 (mEq/L), the calcium of 0.0-about 4.0 (mEq/L), the magnesium of 0-about 4.0 (mEq/L).
In a kind of embodiment preferred, lactate adds within the scope that the bicarbonate sum is 20-about 45 (mEq/L).
Advantage of the present invention is the peritoneal dialysis solution that it provides a kind of improvement.
Furthermore, advantage of the present invention is that the penetrating agent of its a kind of improvement of providing is used in the peritoneal dialysis solution.
Other advantage of the present invention is that the dialysis solution that it provides is allowed lasting ultrafiltration in long residence time.
Advantage of the present invention or even it provide a kind of coalition big and little molecular weight solute.
An advantage of the invention is that it provides the selection that increases injection capacity, so that the usefulness that obtains improveing.
Other advantage of the present invention is the coalition that it provides penetrating agent, so that the safety that obtains improveing.
Furthermore, advantage of the present invention is that the abdominal cavity that it provides calorie (heat) and nitrogenous source to balance each other replenishes, so that the improvement nutritional status.
Moreover advantage of the present invention is that it provides the solution that possesses the physiology pH value, helps to reduce pain when the patient injects peritoneal dialysis solution.
And advantage of the present invention is that it provides the osmolality that reduces along with physiological PH value, so that recover the peritoneal cell function.
Other advantages of the present invention and characteristics, apparent, will in the narration part of representing preferred embodiment and accompanying drawing, obtain explanation.
Description of drawings
The graphic explanation of Fig. 1 obtains the scattergram of abdomen inner capacities to the solution time according to following test.
The graphic explanation of Fig. 2 obtains the scattergram of abdomen inner capacities to the solution time according to following test.
The graphic explanation of Fig. 3 is according to the absorbance percent of the individually dosed maltodextrin of following test.
The graphic explanation of Fig. 4 is according to following test maltodextrin and aminoacid the absorbance percent of administration together.
The graphic explanation of Fig. 5 is according to the performance of following testing liquid.
Represent preferred version to describe in detail
Improvement peritoneal dialysis solution provided by the invention preferably comprises maltodextrin and aminoacid is made penetrating agent.This dialysis solution preferably includes the aminoacid of accurate setting and the penetrating agent that the maltodextrin mixture is used as peritoneal dialysis solution.
As hereinafter describing in detail, utilize aminoacid and maltodextrin to make the penetrating agent of peritoneal dialysis solution, overcome the shortcoming of conventional penetrating agent.The penetrating agent that maltodextrin and aminoacid provide makes it possible to provide a kind of coalition of high and low molecular weight solutes.Preferably utilize the maltodextrin of necessary and nonessential ispol and the about 2-6% (w/v) of about 0.25-2% (w/v) as penetrating agent.
Used maltodextrin is preferably derived from the starch hydrolysis.Maltodextrin preferably has following composition:
Weight average molecular weight (Mw) 10000-16000 dalton
Number-average molecular weight (Mn) 4000-8000 dalton
Dispersion polymerization 1.0-4.0
Fraction＞100000 dalton NMT 1.0%
List, two, trisaccharide NMT 5.0%
It is normal to distribute
α(1-4) NLT 90％
Aluminum (10% solution)＜10ppb
Water solubility NLT 10% (w/v)
PH (10% solution) 5.0-7.0
Heavy metal＜5ppm
DP (degree of polymerization) is greater than 20 〉=75%
DP is greater than 40 〉=50%
DP is greater than 80 〉=25%
Except that maltodextrin, solution preferably contains and must form with nonessential amino acid whose mixture and by following:
Amino acid concentration (mg%)
Leucine 74-112
Valine 100-151
Threonine 47-71
Isoleucine 61-92
Lysine hydrochloride 55-83
Histidine 52-78
Methionine 32-48
Phenylalanine 42-62
Tryptophan 20-30
Alanine 68-103
Proline-4 3-65
Arginine 60-113
Glycine 36-55
Serine 48-72
Tyrosine 20-35
Aspartic acid 55-83
Glutamic acid 55-83 preferred proportion:
Phenylalanine/tyrosine 1.3-3.0
Necessary/total amount aminoacid 0.4-0.7
Although preferred maltodextrin and aminoacid are as penetrating agent, other height and low-molecular-weight compositions still can be used in combination.Can think that its weight average molecular weight of high-molecular weight compositions should be more than or equal to 10000 Doltons.The molecular weight of low-molecular-weight compositions should be less than or equal to 300 Doltons.The molecular weight that these compositionss preferably have is respectively within following scope: about 10000-16000 Dolton; With about 100-300 Dolton.
As non-limiting example, now solution embodiment of the present invention is listed below:
Maltodextrin (%w/v) 2.0-6.0
Aminoacid (%w/v) 0.25-2.0
Sodium (mEq/L) 120-140
Chloride (mEq/L) 70-110
Lactate (mEq/L) 0.0-45.0
Bicarbonate (mEq/L) 0.0-45.0
Calcium (mEq/L) 0.0-4.0
Magnesium (mEq/L) 0.0-4.0
pH 6.0-7.4
In the last example, composition incompatible with each other can separately mix before the infusion when sterilization.As non-limiting example, compositions can be contained in isolated case chamber or the container, and is as follows:
1 case chamber, case chamber 2
Maltodextrin (%w/v) 2-6.0
Aminoacid (%w/v) 0.0 0.25-2.0
Sodium (mEq/L) 0-300 0-300
Chloride (mEq/L) 0-250 0-250
Lactate (mEq/L) 0-100 0-100
Bicarbonate (mEq/L) 0-100 0-100
Calcium (mEq/L) 0-10 0-10
Magnesium (mEq/L) 0-5.0 0-5.0
pH 4.0-5.5 6.0-7.5
Only contain maltodextrin in the preferred case chamber 1.In a kind of embodiment, lactate is contained in case chamber 1 with maltodextrin.
Each composition of two casees chambers is mixed before injecting the patient abdominal cavity.
As non-limiting example, the animal model of peritoneal dialysis is presented below.By animal model as seen, to flow to the patient for fluid and solute through peritoneal dialysis be ideal to the solution that contains big solute (mw 10000-16000 Dolton) and little solute (molecular weight 100-300 Dolton) coalition.Also suggestion of this experiment contains in conjunction with the solution of penetrating agent more effective than the solution that respectively contains independent penetrating agent.The maltodextrin that limits compositions as the present invention as big solute with by top when using for certainty ratio aminoacid, observe the effect of dialytic efficiency beyond expectation in long residence time, this dialytic efficiency decides with the ultrafiltration (UF) of penetrating agent that every gram is absorbed.Referring to Fig. 5.No. 1 embodiment foreword
The maltodextrin of different weight average molecular weight is substituted penetrating agent as the selection of dextrose, study to the normal mice administration with peritoneal dialysis solution.Also carry out other experiment with bonded maltodextrin/aminoacid.Material preparation
Use the maltodextrin powder of different enzyme hydrolysis degree to carry out these experiments.
Preparation 5% (w/v) solution is also analyzed molecular weight, osmolality and pH, and is as follows:
Sample ID weight average molecular weight Mw osmolality (mOsm/kg) pH
G6 38000 17 5.3
G17 12700 38 5.1
G29 2400 65 5.2
G40 2000 103 5.3
G17D 21600 30 5.1
G29D 3400 44 5.2
Prepare aminoacid separately, be expressed as follows by weight percentage: Leu 8.45%; Val 12.27%; Thr 5.36%; Ile 7.00%; Lys 5.45%; His 5.91%; Met 3.64%; Phe 4.73%; Trp 2.27%; Ala 7.73%; Pro 4.91%; Arg 6.82%; Gly 4.18%; Ser 5.45%; Tyr 2.73%; Asp 6.55% and Glu 6.55%.
Table 1 has been summed up the independent ingredients of maltodextrin or with the situation of aminoacid ingredients.Make all solution composition dissolvings, filter by 0.22 μ m filter sterilised then and enter Viaflex Bag. 14The normal saline of C dextran injects each solution bag (1 μ Ci/30ml) as diluting labelling to measure the abdomen inner capacities.
The pH of analytical solution, osmolality, sodium and chloride.
Table 1
The composition of maltodextrin dialysis solution
7.5％G170 7.5％G17 7.5％G29D
Composition
Maltodextrin (g/L) 75 75 75
Aminoacid admixture (g/L)
Goal object
Sodium (mEq/L) 132 132 132
Chloride (mEq/L) 96 95 96
Lactate (mEq/L) 40 40 40
Calcium (mEq/L) L) 3.5 3.5 3.5
Magnesium (mEq/L) 0.5 0.5 0.5
Electrolyte total amount (mEq/L) 272 272 272
Analyze composition
Osmolality (mOsm/kg) 302 322 352
pH 5.1 5.1 5.1
Sodium (mEq/L) .) 126 125 126
Chloride (mEq/L) 96 96 96
Maltodextrin GPC
Mean molecule quantity Wt. 21.500 12.700 3.400
7.5％G29 3％G170/ 0.75％AAs 3％G17/ 0.75％AAs
Composition
Maltodextrin (g/L) 75 30 30
Aminoacid admixture (g/L) 7.5 7.5
Goal object
Sodium (mEq/L) 132 132 132
Chloride (mEq/L) 95 96 96
Lactate (mEq/L) 40 40 40
Calcium (mEq/L) 3.5 3.5 3.5
Magnesium (mEq/L) 0.5 0.5 0.5
Electrolyte total amount (mEq/L) 272 272 272
Analyze composition
Osmolality (mOsm/kg) 374 327 333
pH 5.1 7.0 7.0
Sodium (mEq/L)) 126 123 126
Chloride (mEq/L) 96 93 96
Maltodextrin GPC
Mean molecule quantity Wt 2.400 21.600 12.700
3％ G29D/ 0.75％ AAs 1％ AA 4％ G170/1％ AAs 4％ G17/ 1％ AAs
Composition
Maltodextrin (g/L) 30 40 40
Aminoacid admixture (g/L) 7.5 10 10 10
Goal object
Sodium (mEq/L) 132 132 132 132
Chloride (mEq/L) 96 96 96 96
Lactate (mEq/L) 40 40 40 40
Calcium (mEq/L) 3.5 3.5 3.5 3.5
Magnesium (mEq/L) 0.5 0.5 0.5 0.5
Electrolyte total amount (mEq/L) 272 272 272 272
Analyze composition
Osmolality (mOsm/kg) 342 335 360 370
pH 7.0 7.0 7.0 7.0
Sodium (mEq/L) 130 132 131 132
Chloride (mEq/L) 100 99 99 100
Maltodextrin GPC
Mean molecule quantity Wt. 3.400 21.600 12.700
Experimental arrangement 7.5% maltodextrin is individually dosed
(Indiana) heavy 300-370 gram is at two maltodextrin solutions (n=6/ group) of handling administration 7.5% (w/v) in day process for Harlan Sprague Dawley Inc., Indianapolis for the male Mus of Sprague-Dawley.Before solution injects, gather the 1.5ml baseline blood samples through the tail vein.Under the 12000xg condition, go out blood plasma and stored frozen through centrifugalize in 10 minutes.
During given disposal day, earlier every Mus is weighed, the anesthesia of Metafane inhalation shaves off ventral seta, with injecting dialysis solutions (90ml/kg) in No. 23 needle tubing abdomens.Before injecting dialysis solution is warmed to room temperature.Dialysis solution (25-35ml) contains about 1 μ Ci's 14The C dextran is made the dilution labelling to measure the abdomen inner capacities.
Make the Mus recovery and allow that its freedom is near water.The the 2nd and 4 hour collection dialysis solution sample (0.2ml) and freezing during resident.The blood sample of also gathering 2 hours is with the dialysis solution of measuring urine and the kreatinin ratio (D/P) to blood plasma.
In the latter stage in 8 hour resident cycle, adopt the 2ml blood sample through arteria caudalis, separate and frozen plasma.It is till death painless with Mus that the tail vein injects T-61 solution.Open the abdominal cavity with midline incision immediately, collect the dialysis solution and the recording capacity of weighing.Stored frozen 5ml dialysis solution sample is equipped with further to be analyzed.3% maltodextrin/0.7% aminoacid
Carry out dialysis procedure as described above, use the Sprague-Dawley Mus of heavy 270-400 gram.During two disposal days, offer medicine to Mus with 3% maltodextrin/0.75% Freamine or 4.25% dextrose (Dextrose Dianeal) solution (n=6/ group).4% maltodextrin/1% aminoacid
By the aforementioned dialysis procedure that carries out, use the heavy 350-380 gram Mus of Sprague-Dawley company.During two disposal days, offer medicine to Mus with 4% maltodextrin/1% Freamine or independent 1% aminoacid (n=6/ group).The sample analysis osmolality
In depression of the freezing point mode all dialysis solution are all surveyed its osmolality.[instrument Osmometer Advanced Instrument Model (3MO)] 14The C dextran
All dialysis solution samples carry out the analysis of dextrose radio-labeled.With 0.1 or the dialysis solution sample of .05ml add in the 1ml water that is contained in the 7ml glass scintillation pipe.Add the ReadyGel flicker mixture (Beckman) of 3ml and rock scintillation vial up to gel.The instrument of sample counting is Beckman Scintillation Counter Model LS 5000 TD.Maltodextrin
With enzyme hydrolysis go on a tour from glucose mode analysis of experiments fresh with malto-dextrin contg exhausted dialysis solution sample.The 0.01M sodium acetate solution that with 950 μ L concentration is 0.6mg/ml dextrin glycosidase is in 55 ℃ of incubations, 50 μ L dialysis solution samples.Then with the glucose of following methods analyst hydrating solution: hexokinase catalysis glucose phosphorylation.In the coupling reaction, with glucose-6-phosphate dehydrogenase (G6PD) catalysis, NAD is reduced into NADH.The change of gained absorbance is directly proportional with concentration of glucose.The BUN/ kreatinin
Analysed for plasma and dialysis solution sample on Boehringer Mannheim/Hitachi 704 analysers.
BUN: by urine enzyme effect hydrolysis urine.In the coupling reaction, NADH is oxidized to NAD.The change of gained absorbance is directly proportional with urine concentration.
Kreatinin/Pap: creatininase changes into creatine with kreatinin.Kreatinase changes into sarcosine with creatine.Sarcosine oxidase makes the sarcosine oxidation produce hydrogen peroxide and is used in the indicator reaction to form red benzoquinone imine dyestuff mode.The result
Descend column count according to sample analysis: net ultrafiltration
Difference during according to injection capacity and dialysis end in 8 hours between the capacity is measured 8 hours resident net ultrafiltrations of all Mus.The abdomen inner capacities
During resident 14The C dextrose is from the dialysis solution estimator of the 2nd and 4 hour dialysis solution capacity of taking temperature that disappears.Abdomen inner capacities estimator when fixing time t according to following equation: Vt = DPMin - [ DPMin - DPMout ] * t 8 Ct / W Wherein: DPM in=injection capacity -14C dextrose concentration.
DPM out=was in 8 hours drain capacity -14C dextrose concentration.
During Ct=time t 14C dextrose concentration.
W=body weight (kg).
The graphic explanation capacity of Fig. 1 and Fig. 2 distributes.2.5% dextrose Dianeal (n=11) capacity of previous research distributes and is comprised with existing data.The dialysis solution osmolality
Measure the 2nd, 4 and 8 hour osmolality result.The absorbance of penetrating agent
Measure the absorbance (%) of each interval with following equation: [ Vo * Co ] - [ Vt * Ct ] * 100 [ Vo * Co ] Wherein: Vo=injection capacity (ml)
Penetrating agent concentration (g/dl) during Co=(t=0)
Capacity (ml) during Vt=time t
Concentration (g/dl) during Ct=time t
Attention: capacity was based in the 2nd and 4 hour 14C dextran dilution factor is estimated.
The percent absorption of measuring with coalition administration maltodextrin in 8 hours.The result
This institute is got data carry out the Tukey statistical analysis.As the cell mean that is shown in α=0.05 o'clock mensuration has statistical significance.Average under the same line there is no marked difference. Wherein: 1=7.5% G17D2=7.5% G173=7.5% G29D4=7.5% G295=4% G17D+1% AA6=4% G17+1% AA7=2.5% dextrose conclusion
The graphic result that illustrated of Fig. 1-5.
When individually dosed, although the initial osmolality of comparing with 2.5% Dianeal is lower, 8 hours drain capacity of glucose polymer is increased.Adding 1% aminoacid makes and obtains the 8 hours needed glucose polymer quantity of the clean UF of equivalence and reduce 46%.
When comparing separately with glucose, obviously reduces the absorption percent of 8 hours last glucose polymers.Adding aminoacid does not change the percent of the glucose polymer of absorption.It is higher that coalition solution (GP+ aminoacid) then obtains the clean UF of the penetrating agent that every gram absorbs.
Should understand, those skilled in the art can make many changes and improvements to representative preferred embodiment described herein, and it does not deviate from or exceed spirit and scope of the invention, also do not reduce attendant advantages.Because claims that these changes and improvements have been applied cover.

Claims (22)

1. peritoneal dialysis solution, this solution comprises the maltodextrin of about 2.0-6.0% (w/v); With the aminoacid of about 0.25-2.0% (w/v) as a kind of penetrating agent, wherein said maltodextrin has following feature:
Weight average molecular weight (Mw) 10000-16000 dalton
Number-average molecular weight (Mn) 4000-8000 dalton
Dispersion polymerization 1.0-4.0
Fraction＞100000 dalton NMT 1.0%
List, two, trisaccharide NMT 5.0%
It is normal to distribute
α(1-4) NLT 90％
Aluminum (10% solution)＜10ppb
Water solubility NLT 10% (w/v)
PH (10% solution) 5.0-7.0
Heavy metal＜5ppm
DP (degree of polymerization) is greater than 20 〉=75%
DP is greater than 50 〉=50%
DP is greater than 100 〉=25%.
2. according to the peritoneal dialysis solution of claim 1, wherein aminoacid comprises essential and non essential amino acid.
3. according to the peritoneal dialysis solution of claim 1, wherein said solution further comprises sodium, chloride, lactate, bicarbonate, calcium and magnesium.
4. according to the peritoneal dialysis solution of claim 1, wherein this solution further comprises:
Sodium (mEq/L) 120-about 140
Chloride (mEq/L) 70-about 110
Lactate (mEq/L) 0-about 45.00
Bicarbonate (mEq/L) 0-about 45.00
Calcium (mEq/L) 0-about 4.00
Magnesium (mEq/L) 0-about 4.00.
5. according to the peritoneal dialysis solution of claim 1, its pH value is about 6.0-7.4.
6. peritoneal dialysis solution, this solution comprise about 2.0-6.0% (w/v) maltodextrin and approximately 0.25-2.0% (w/v) aminoacid is as a kind of penetrating agent, and wherein aminoacid comprises:
Amino acid concentration (mg%)
Leucine 74-112
Valine 100-151
Threonine 47-71
Isoleucine 61-92
Lysine hydrochloride 55-83
Histidine 52-78
Methionine 3248
Phenylalanine 42-62
Tryptophan 20-30
Alanine 68-103
Proline-4 3-65
Arginine 60-113
Glycine 36-55
Serine 48-72
Tyrosine 20-35
Aspartic acid 55-83
Glutamic acid 55-83.
7. according to the peritoneal dialysis solution of claim 6, maltodextrin wherein has following composition:
Weight average molecular weight (Mw) 10000-16000 dalton
Number-average molecular weight (Mn) 4000-8000 dalton
Dispersion polymerization 1.0-4.0
Fraction＞100000 dalton NMT 1.0%
List, two, trisaccharide NMT 5.0%
It is normal to distribute
α(1-4) NLT 90％
Aluminum (10% solution)＜10ppb
Water solubility NLT 10% (w/v)
PH (10% solution) 5.0-7.0
Heavy metal＜5ppm
DP (degree of polymerization) is greater than 20 〉=75%
DP is greater than 50 〉=50%
DP is greater than 100 〉=25%.
8. according to the peritoneal dialysis solution of claim 6, maltodextrin wherein is deutero-by the starch hydrolysis.
9. according to the peritoneal dialysis solution of claim 1, wherein select aminoacid to have following ratio:
Phenylalanine/tyrosine 1.3-3.0
Essential/total amount aminoacid 0.4-0.7.
10. according to the peritoneal dialysis solution of claim 1, wherein maltodextrin and aminoacid constitute unique penetrating agent component.
11. a peritoneal dialysis solution, this solution comprises:
Maltodextrin (%w/v) 2.0-6.0
Aminoacid (%w/v) 0.25-2.0
Sodium (mEq/L) 120-140
Chloride (mEq/L) 70-110
Lactate (mEq/L) 0.0-45.0
Bicarbonate (mEq/L) 0.0-45.0
Calcium (mEq/L) 0.0-4.0
Magnesium (mEq/L) 0.0-4.0
PH 6.0-7.4; Be characterised in that with maltodextrin the DP of maltodextrin (degree of polymerization) will make:
DP＞20 ≥75％
DP＞40 50％
DP＞80 ≥25％。
12. according to the peritoneal dialysis solution of claim 11, maltodextrin wherein is deutero-by the starch hydrolysis, and has following composition:
Weight average molecular weight (Mw) 10000-16000 dalton
Number-average molecular weight (Mn) 4000-8000 dalton
Dispersion polymerization 1.0-4.0
Fraction＞100000 dalton NMT 1.0%
List, two, trisaccharide NMT 5.0%
It is normal to distribute
α(1-4) NLT90％
Aluminum (10% solution)＜10ppb
Water solubility NLT 10% (w/v)
PH (10% solution) 5.0-7.0
Heavy metal＜5ppm
DP (degree of polymerization) is greater than 20 75%
DP is greater than 50 〉=50%
DP is greater than 100 〉=25%.
13. according to the peritoneal dialysis solution of claim 11, wherein aminoacid comprises:
Amino acid concentration (mg%)
Leucine 74-112
Valine 100-151
Threonine 47-71
Isoleucine 61-92
Lysine hydrochloride 55-83
Histidine 52-78
Methionine 32-48
Phenylalanine 42-62
Tryptophan 20-30
Alanine 68-103
Proline-4 3-65
Arginine 60-113
Glycine 36-55
Serine 48-72
Tyrosine 20-35
Aspartic acid 55-83
Glutamic acid 55-83.
14., wherein select aminoacid to have following ratio according to the peritoneal dialysis solution of claim 11:
Phenylalanine/tyrosine 1.3-3.0
Essential/total amount aminoacid 0.4-0.7.
15. according to the peritoneal dialysis solution of claim 11, wherein maltodextrin and aminoacid constitute unique penetrating agent component.
16. a method for preparing the penetrating agent that is used for peritoneal dialysis solution, this method comprises the following step:
Selection is as the step of first kind of component of penetrating agent, the molecular weight that first kind of component has be equal to or greater than 10000 dalton and constitute dialysis solution about 2.0-6.0% (w/v) and
Selection is as second kind of component of penetrating agent, and the molecular weight that second kind of component has is equal to or less than 300 dalton and constitutes about 0.25-2.0% (w/v) of dialysis solution.
17. according to the method for claim 16, penetrating agent wherein comprises maltodextrin and aminoacid.
18. according to the method for claim 17, maltodextrin wherein is deutero-by the starch hydrolysis, and has following composition:
Weight average molecular weight (Mw) 10000-16000 dalton
Number-average molecular weight (Mn) 4000-8000 dalton
Dispersion polymerization 1.0-4.0
Fraction＞100000 dalton NMT 1.0%
List, two, trisaccharide NMT 5.0%
It is normal to distribute
α(1-4) NLT 90％
Aluminum (10% solution)＜10ppb
Water solubility NLT 10% (w/v)
PH (10% solution) 5.0-7.0
Heavy metal＜5ppm
DP (degree of polymerization) is greater than 20 〉=75%
DP is greater than 50 〉=50%
DP is greater than 100 〉=25%.
19. according to the method for claim 17, aminoacid wherein comprises:
Amino acid concentration (mg%)
Leucine 74-112
Valine 100-151
Threonine 47-71
Isoleucine 61-92
Lysine hydrochloride 55-83
Histidine 52-78
Methionine 32-48
Phenylalanine 42-62
Tryptophan 20-30
Alanine 68-103
Proline-4 3-65
Arginine 60-113
Glycine 36-55
Serine 48-72
Tyrosine 20-35
Aspartic acid 55-83
Glutamic acid 55-83.
20. a two-part peritoneal dialysis solution, this solution is decided to be before the patient injects and mixes, and this solution comprises:
The first of taking in first kind of device comprises about 2.0-6.0% (w/v) maltodextrin and the about 4.0-5.5 of pH value;
The second portion of taking in second kind of device comprises aminoacid; With
Not only can but also can in second kind of device, comprise the following ingredients of q.s at first kind of device, like this, it is as follows to obtain ingredients when first and second portion mixing: the sodium of 120-about 140 (mEq/L), the chloride of about 70.0-110.00 (mEq/L), the lactate of about 0.0-5.0 (mEq/L), the bicarbonate of about 0.0-45.0 (mEq/L), the magnesium of the calcium of 0.0-about 4.0 (mEq/L) and 0.0-about 4.0 (mEq/L).
21. according to a kind of two-part peritoneal dialysis solution of claim 20, wherein first and second kinds of devices are two isolated case chambers at a container.
22. according to a kind of two-part peritoneal dialysis solution of claim 20, the pH of gained solution that wherein comprises the mixture of first and second portion is about 6.0-7.4.
CN95190042A 1994-01-21 1995-01-23 Peritoneal dialysis solutions containing maltodextrins and amino acids Expired - Fee Related CN1091602C (en)

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